Nine patients with Rheumatoid Arthritis, unresponsive to conventional therapy, have been studied in an open trial of a short course of lymphapheresis (six procedures over two to three weeks). Immunologic characteristics of the mononuclear cells removed do not correlate with initial disease activity. However, diminished mononuclear cell reactivity to various stimuli, in general, predicted a favorable response to therapy. Abnormalities tended to resolve with therapy. Nonresponders generally exhibited normal reactivity. Clinical improvement was quite variable in degree and frequently short term. These studies into potential mechanisms of disease in rheumatoid arthritis and provide new data with which to assess apheresis as a therapeutic modality.